3-amino-1-oxo-2-phenyl-5-(pyrrolidin-1-yl)-1,2,4a,5,6,7,8,9-octahydropyrimido[1,6-a]azepine-4-carbonitrile | 1233944-05-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环庚烷
• 英文名称: 3-amino-1-oxo-2-phenyl-5-(pyrrolidin-1-yl)-1,2,4a,5,6,7,8,9-octahydropyrimido[1,6-a]azepine-4-carbonitrile
• 英文别名: 3-amino-1-oxo-2-phenyl-5-pyrrolidin-1-yl-4a,5,6,7,8,9-hexahydropyrimido[1,6-a]azepine-4-carbonitrile
• CAS: 1233944-05-2
• 化学式: C₂₀H₂₅N₅O
• 分子量: 351.451
• InChiKey: AKXWPCFXKWCPJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  76.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-amino-1-oxo-2-phenyl-5-(pyrrolidin-1-yl)-1,2,4a,5,6,7,8,9-octahydropyrimido[1,6-a]azepine-4-carbonitrile 在 formamide 作用下， 反应 2.0h， 以54%的产率得到1-amino-5-phenyl-12-(pyrrolidin-1-yl)-5,6,8,9,10,11,12,12a-octahydropyrimido[4',5':4,5]pyrimido[1,6-a]azepin-6-one
  参考文献：
  名称：

  Potential anti-inflammatory activity and ulcerogenicity study of some novel pyrimido[4′,5′:4,5]pyrimido[1,6-a]azepine derivatives

  摘要：

  A series of novel tricyclic pyrimido[4',5':4,5]pyrimido[1,6-a]azepine derivatives were synthesized using the starting compound 3-amino-1-oxo-2-phenyl-5-(pyrrolidin-1-yl)-1,2,4a,5,6,7,8,9-octahydropyrimido[1,6-a]azepine-4-carbonitrile 4. This series includes the 3-aryl derivatives 6a, b, the 3-cycloaminoalkyl derivatives 8a-f, the 3-mercaptomethyl derivatives 10 and 11a, b, the 2-cycloaminomethyl derivatives 13a-c, the 1-cycloamino derivatives 15a-c and the 1-amino derivative 16. The structures of the newly synthesized compounds were elucidated by IR, H-1 NMR, C-13 NMR, mass spectroscopy and elemental analyses. The anti-inflammatory activity of all newly synthesized compounds was evaluated using the carrageenan-induced paw oedema test in rats using diclofenac sodium as the reference drug. Ulcer indices for the most active compounds were calculated. The 3-mercaptomethylacetic acid derivative 10 was the most active compound, showing activity comparable to diclofenac sodium with minimal ulcerogenic effect while the rest of the tested compound exhibited moderate anti-inflammatory activity.

  DOI：

  10.1007/s00044-010-9545-5
• 作为产物：
  描述：

  在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 生成 3-amino-1-oxo-2-phenyl-5-(pyrrolidin-1-yl)-1,2,4a,5,6,7,8,9-octahydropyrimido[1,6-a]azepine-4-carbonitrile
  参考文献：
  名称：

  Potential anti-inflammatory activity and ulcerogenicity study of some novel pyrimido[4′,5′:4,5]pyrimido[1,6-a]azepine derivatives

  摘要：

  A series of novel tricyclic pyrimido[4',5':4,5]pyrimido[1,6-a]azepine derivatives were synthesized using the starting compound 3-amino-1-oxo-2-phenyl-5-(pyrrolidin-1-yl)-1,2,4a,5,6,7,8,9-octahydropyrimido[1,6-a]azepine-4-carbonitrile 4. This series includes the 3-aryl derivatives 6a, b, the 3-cycloaminoalkyl derivatives 8a-f, the 3-mercaptomethyl derivatives 10 and 11a, b, the 2-cycloaminomethyl derivatives 13a-c, the 1-cycloamino derivatives 15a-c and the 1-amino derivative 16. The structures of the newly synthesized compounds were elucidated by IR, H-1 NMR, C-13 NMR, mass spectroscopy and elemental analyses. The anti-inflammatory activity of all newly synthesized compounds was evaluated using the carrageenan-induced paw oedema test in rats using diclofenac sodium as the reference drug. Ulcer indices for the most active compounds were calculated. The 3-mercaptomethylacetic acid derivative 10 was the most active compound, showing activity comparable to diclofenac sodium with minimal ulcerogenic effect while the rest of the tested compound exhibited moderate anti-inflammatory activity.

  DOI：

  10.1007/s00044-010-9545-5

文献信息

• Synthesis, anti-inflammatory and ulcerogenicity studies of some substituted pyrimido[1,6-a]azepine derivatives
  作者：Nehad A. El-Sayed、Fadi M. Awadallah、Nashwa A. Ibrahim、Mohammed T. El-Saadi

  DOI：10.1016/j.ejmech.2010.04.005

  日期：2010.7

  New series of pyrimido[1,6-a]azepines were prepared through reaction of the key amino compound 4 with various reagents to give a variety of 3-N-substituted amino derivatives 5–13. The synthesized compounds included the Mannich bases 5a–c, the formimidic acid ester 6, the phenylformamidines 7a–c, the benzylidine amino derivatives 8a–c, the acetic acid derivatives 9, 10a–c and 11, the carbamoylformates

  通过氨基化合物键的反应，制备新系列嘧啶并[1,6-α]氮杂的4与各种试剂，从而提供多种的3-N-取代的氨基衍生物5 - 13。合成的化合物包括曼尼希碱5A - Ç，所述formimidic酸酯6中，phenylformamidines 7A - Ç中，苯亚甲基氨基的衍生物8A - Ç，乙酸衍生物9，图10A - Ç和11，所述carbamoylformates 12a中，b和酰胺类13a，b。使用双氯芬酸钠作为参比药物，使用角叉菜胶诱导的大鼠足水肿筛选所有化合物的抗炎活性。此外，还计算出活性最高的化合物的溃疡指数。化合物3，4，图8a，Ç，11和12a中，b显示出活性比用没有或最小胃溃疡双氯芬酸钠类似或更高。没有溃疡作用的最具活性的化合物是氨基衍生物4（IC 50 = 6.61 mmol / kg）。
• Potential anti-inflammatory activity and ulcerogenicity study of some novel pyrimido[4′,5′:4,5]pyrimido[1,6-a]azepine derivatives
  作者：Nehad A. El-Sayed、Fadi M. Awadallah、Nashwa A. Ibrahim、Mohamed T. El-Saadi

  DOI：10.1007/s00044-010-9545-5

  日期：2012.3

  A series of novel tricyclic pyrimido[4',5':4,5]pyrimido[1,6-a]azepine derivatives were synthesized using the starting compound 3-amino-1-oxo-2-phenyl-5-(pyrrolidin-1-yl)-1,2,4a,5,6,7,8,9-octahydropyrimido[1,6-a]azepine-4-carbonitrile 4. This series includes the 3-aryl derivatives 6a, b, the 3-cycloaminoalkyl derivatives 8a-f, the 3-mercaptomethyl derivatives 10 and 11a, b, the 2-cycloaminomethyl derivatives 13a-c, the 1-cycloamino derivatives 15a-c and the 1-amino derivative 16. The structures of the newly synthesized compounds were elucidated by IR, H-1 NMR, C-13 NMR, mass spectroscopy and elemental analyses. The anti-inflammatory activity of all newly synthesized compounds was evaluated using the carrageenan-induced paw oedema test in rats using diclofenac sodium as the reference drug. Ulcer indices for the most active compounds were calculated. The 3-mercaptomethylacetic acid derivative 10 was the most active compound, showing activity comparable to diclofenac sodium with minimal ulcerogenic effect while the rest of the tested compound exhibited moderate anti-inflammatory activity.